动物造模 z-bio 2022-07-21 281

　　Objective: To use SD rats as a model to observe the effects of pre-pregnancy ethinyl estradiol exposure on the changes of glucose metabolism in offspring and the expression of genes related to glucose metabolism in the liver.

　　METHODS: Fifty-two female rats were randomly divided into 4 groups: control group (sesame oil), 50, 200, and 800 μg/kg EE groups, once a day, and conceived after 15 days of continuous gavage exposure. Oral glucose tolerance (OGTT) and insulin tolerance (ITT) tests were performed on the 23rd day (postnatal day, P23) and P25, respectively, and the expression levels of glucose metabolism-related genes in the liver were detected by RT-PCR.

　　Results: The OGTT of offspring female mice: the fasting blood glucose value of the 200μg/kg EE group was significantly lower than that of the control group (P < 0.05); the 15-min blood glucose value of the 800μg/kg EE group was significantly higher than that of the control group, 50 μg/kg EE group (P < 0.05). P < 0.01, P < 0.01, P < 0.01), the 2 h blood glucose levels in the 50 and 800 μg/kg EE groups were significantly lower than those in the control group (P < 0.05, P < 0.01). OGTT of offspring male rats: at the 15th minute, the blood glucose value of the 800μg/kg EE group was significantly higher than that of the control group (P < 0.01); at the 30th minute, the blood glucose value of the 200μg/kg EE group was significantly lower than that of the control group (P < 0.05). ). ITT of offspring female mice: At the 15th minute, the blood glucose levels in the 50 and 200 μg/kg EE groups were significantly higher than those in the control group (P < 0.001, P < 0.01). ITT of offspring male rats: At 30 min, the blood glucose levels in the 50 and 200 μg/kg EE groups were significantly higher than those in the control group (P < 0.01, P < 0.01). RT-PCR of offspring female mice: Glut2 and Lpk mRNA expression levels in 50, 200 μg/kg EE and 800 μg/kg EE groups were significantly lower than those in control group (P < 0.01, P < 0.05, P < 0.05); 50, 200 μg/kg EE The expression level of Gys2 mRNA in the group was significantly lower than that in the control group (P < 0.01, P < 0.01). RT-PCR of offspring male mice: the expression levels of G6pase and Pepck mRNA in the 200μg/kg EE group were significantly higher than those in the control group (P < 0.01, P < 0.01), and the expression levels of Glut2 mRNA in the 50μg/kg EE group were significantly lower than those in the control group (P < 0.01, P < 0.01). P < 0.01), the expression level of Gys2 mRNA in the 800μg/kg EE group was significantly higher than that in the control group (P < 0.01).

　　Conclusion: Pre-pregnancy exposure to ethinyl estradiol can lead to impaired glucose tolerance, insulin resistance and abnormal expression of genes related to glucose metabolism in the liver of offspring female mice. Moreover, these effects were sex-differenced, and offspring female mice were more sensitive to pre-pregnancy EE exposure.